tbuckley/cabot-search huggingface dataset:
Assessment of treatment patterns and real-world outcomes following changes in the treatment paradigm for locally advanced/metastatic urothelial carcinoma (la/mUC) in the US.
Authors: Melissa Kirker, Anup Abraham, Anna Vlahiotis, Abhijeet Bhanegaonkar, Darrin Benjumea, Chai Kim, Haiyan Sun, Mairead Kearney, Sanjana Chandrasekar, Benjamin Li, Sheena Thakkar, Helen H Moon
Journal: Journal of Clinical Oncology (2023)

468 Background: The standard-of-care first-line (1L) treatment for la/mUC is platinum-based chemotherapy (PBC) followed by avelumab 1L maintenance (1LM) in those who have not progressed following 1L PBC. This study aims to understand treatment patterns and real-world outcomes in patients with la/mUC in the US, including the early adoption of avelumab 1LM since its FDA approval in June 2020. Methods: Patients aged ≥18 years diagnosed with la/mUC between Jan 2015 and Jul 2021 were identified using electronic health records from the Flatiron Health database. Patient characteristics at baseline (la/mUC diagnosis) and clinical outcomes were described by 1L treatment received using the Kaplan-Meier method. Results: Of 4,387 patients included in this study, 3,706 (84.5%) received systemic treatments. Cisplatin-based therapy was the most common 1L therapy (33.3%), followed by carboplatin-based (30.9%) and immuno-oncology (IO) therapies (28.0%). Patients treated with cisplatin-based therapies had longer median progression-free survival compared with patients treated with carboplatin-based and IO therapies (8.0, 6.4, and 6.1 months, respectively). Median overall survival (mOS) in the treated cohort was 14.6 months from the initiation of 1L therapy. Patients treated with 1L cisplatin-based therapies had the longest mOS (18.3 months), followed by 1L IO therapies (14.6 months), and 1L carboplatin (13.2 months). Since July 2020, 89 patients received avelumab 1LM; the median follow-up time from the start of 1LM avelumab was 6.0 months and clinical outcomes data were immature. Of 1L-treated patients, 50.6% (n=1,874) moved onto second-line (2L) therapy during the study period. Notably, the cohort with the lowest 2L treatment rates were patients treated with 1L IO. The table demonstrates treatment sequences for this population. Conclusions: In this real-world cohort, most patients received standard-of-care platinum-based chemotherapy in 1L, with those on cisplatin-based therapy demonstrating the best outcomes. Early uptake of avelumab as 1LM was observed, and future analysis should examine the clinical outcomes of patients who received avelumab 1LM following 1L PBC. [Table: see text]
Phase 2, multicenter, open-label basket trial of <i>nab</i>-sirolimus for patients with malignant solid tumors harboring pathogenic inactivating alterations in <i>TSC1</i> or <i>TSC2</i> genes (PRECISION I).
Authors: Gopa Iyer, Michael J. Demeure, Dustin A. Deming, Noah Federman, Meredith McKean, Elizabeth Katherine Lee, Alexander I. Spira, David J. Kwiatkowski, Maen A. Hussein, Erlinda Maria Gordon, David G. Crockett, Kristen N. Ganjoo, Brian Schulte, Lee D. Cranmer, Anita N. Schmid, Willis H. Navarro, Loretta Marie Itri
Journal: Journal of Clinical Oncology (2023)

TPS597 Background: Albumin-bound ( nab)-sirolimus, a novel mTOR inhibitor (mTORi) that utilizes nanoparticle technology to preferentially target tumors, is approved in the US for the treatment of adults with malignant PEComa. In an exploratory analysis of the AMPECT registrational trial of nab-sirolimus in advanced malignant PEComa (NCT02494570), 8/9 (89%) and 1/5 (20%) patients with TSC1 and TSC2 inactivating alterations, respectively, had confirmed response (Wagner, J Clin Oncol. 2021). Importantly, both TSC1 and TSC2 alterations have been observed in patients with various gastrointestinal cancers (Table). Overall, most treatment-related adverse events (TRAEs) in AMPECT were grade 1/2 and manageable for long-term treatment; no grade ≥4 TRAEs occurred. Methods: PRECISION I (NCT05103358) is a phase 2, open-label, multi-institutional basket trial evaluating efficacy and safety of nab-sirolimus in patients with alterations in TSC1 (Arm A) and TSC2 (Arm B). Patients ≥12 years old with malignant solid tumors harboring pathogenic inactivating alterations in TSC1 or TSC2 (confirmed by central review of next-generation sequencing reports) who have progressed on standard therapies and are mTORi-naïve are eligible. nab-Sirolimus 100 mg/m 2 will be administered weekly as an intravenous infusion over 30 minutes on Days 1 and 8 of each 21-day cycle. The primary endpoint is overall response rate determined by independent review using RECIST v1.1; other endpoints include duration of response, disease control rate, time to response progression-free survival by independent radiographic review, overall survival, patient-reported quality of life, and safety. Enrollment is ongoing. The most frequent tumor types expected in this tissue-agnostic trial are bladder, hepatobiliary, endometrial, soft tissue sarcoma, ovarian, and esophagogastric based on the prevalence of TSC1 or TSC2 alterations (Table). Clinical trial information: NCT05103358 . [Table: see text]
Analysis of false-positive biopsy results of PIRADS 4 lesions in multiparametric magnetic resonance imaging of the prostate: Experience from a single nonacademic center using cognitive fusion.
Authors: Augusto C. A. Mota, Bianca Carla Azevedo de Souza, Marco Antonio Soares Novaes, Maria Estela Pompeu do Amaral, Maiara Ferreira de Souza, Daniel Abensur Athanazio
Journal: Journal of Clinical Oncology (2023)

321 Background: Multiparametric magnetic resonance imaging (mpMRI) of the prostate has been increasingly used in the algorithm of the initial diagnosis of patients suspected to harbor prostate cancer (PCa) with the aim of improving the selection of patients who really need a biopsy. Yet patients with PI-RADS 5 lesions almost always have cancer found in their prostates, the same is not true for patients with PI-RADS 4. In this study we sought to describe pathological findings in target biopsies of PI-RADS4, and to identify clinical data that could predict those patients with benign findings. Methods: A retrospective study was conducted in a data bank collected prospectively from December 2015 through April 2022 in a single nonacademic center. The whole series consist of 547 patients, all of whom had a mpMRI of the prostate (reports as per PI-RADS version 2) followed by cognitive fusion prostate biopsy performed by a single, experienced radiologist. All biopsy specimens were read by a specialist in urological pathology. Out of these, 259 had PI-RADS 4 lesion, and 83 had PI-RADS 5. Results: We found a false positive rate of 29% and 3.7% for any cancer in PI-RADS 4 and 5 lesions, respectively. Different histologic patterns were observed among target biopsies. At multivariate analysis, PIRADS lesion ≤ 6 mm and previous negative biopsy were independent predictors of false positive PI-RADS4 lesions. The 76 cases showed normal histology (n = 22), a combination of chronic inflammation, reactive epithelium, and glandular atrophy (n = 18), glandular atrophy (n = 9), stromal proliferation consistent with nodular hyperplasia (n =7), a combination of chronic inflammation, reactive epithelium and glandular atrophy (n = 6), chronic inflammation (n = 4) and HGPIN (n = 10). The small number (n=3) of false PI-RADS5 lesions precluded further analyses. Conclusions: Benign findings are common in PI-RADS4 lesions and most of them did not show obvious glandular or stromal hypercellularity as expected in hyperplastic nodules. Size ≤ 6 mm and previous negative biopsy predict higher probability of false positive results in patients with PI-RADS 4 lesions.[Table: see text]
Germline genetic testing of patients with penile carcinoma.
Authors: Guru P. Sonpavde, Sarah M. Nielsen, Brandie Heald, Kathryn E. Hatchell, Edward D. Esplin, Amin Nassar
Journal: Journal of Clinical Oncology (2023)

10 Background: Penile carcinoma (PeCa) is a rare malignancy with a mean age at diagnosis of 60 years. PeCa is epidemiologically associated with phimosis, HPV, HIV, tobacco, obesity, Psoralen and ultraviolet A photochemotherapy and lichen sclerosis. However, the prevalence and type of pathogenic germline variants (PGVs) associated with PeCa are unknown. Methods: A retrospective cohort of patients (pts) with PeCa who underwent germline testing (range of genes tested, 1-134) from 10/2016 to 5/2022 at a large commercial laboratory (Invitae) was evaluated. Clinician-reported clinical and demographic information from test requisition forms (TRF) were analyzed and the frequency and type of PGVs was determined. Pts were identified via keywords and/or ICD-10 codes for PeCa, but the final study cohort was limited to those whose diagnosis could be corroborated by details in the TRF and/or accompanying medical records. Pts with other pathologies were excluded. Results: Of the 29 pts who met inclusion criteria, the majority were White (65.5%), with a median age (range) of 62.5 years (36-79) at diagnosis. 44.8% of pts had documented squamous cell carcinoma (SCC) pathology, 55.2% of pts had an additional non-PeCa cancer, and 62.1% of pts had a documented family history of relevant cancers (penile, prostate, breast, ovarian, pancreatic and/or colorectal). Among 29 pts with PeCa, 3 harbored PGVs (10.3%) and 16 (55.2%) had &gt; 1 variants of uncertain significance (VUS) in the absence of a PGV. Of the 3 positive pts, 2 harbored BRCA2 PGVs and one harbored a RAD51C PGV. One pt with a BRCA2 PGV had additional malignancies of the prostate and pancreas. Conclusions: This is the first study to our knowledge reporting PGVs in PeCa. PGVs in DNA repair genes ( BRCA2, RAD51C) were identified in 10.3% of selected high-risk PeCa pts with the majority exhibiting other malignancies or family history of malignancies. Larger cohorts of PeCa patients should be studied in pts with different ethnicities. Nonetheless, these data highlight the potential role of germline testing in selected PeCa pts as a tool to aid in clinical management, cascade testing and potential therapeutic relevance in the future.
Lutetium-<sup>177</sup> PSMA radioligand therapy for metastatic castration resistant prostate cancer in Germany: Population-based data with multicenter validation from 2016 to 2020.
Authors: Luka Flegar, Smita George Thoduka, Damiano Librizzi, Markus Luster, Aristeidis Zacharis, Hendrik Heers, Nicole Eisenmenger, Hojjat Ahmadzadehfar, Matthias Eiber, Wolfgang A Weber, Christer Groeben, Johannes Huber
Journal: Journal of Clinical Oncology (2023)

146 Background: Our purpose was to investigate the adoption and current trends of Lutetium- 177 PSMA radioligand therapy (RLT) for metastatic castration-resistant prostate cancer (mCRPC) in Germany. Methods: We analyzed the nationwide German hospital billing database (Destatis) and the hospitals’ quality reports for 177 Lutetium PSMA RLT from 2016 to 2020 using the reimbursement.INFO tool. For detection of trends over time we applied linear regression models. For validation of these billing data, we included a total of 1239 177 Lu-PSMA RLT cycles from 392 patients within the WARMTH multicenter study from 2016 to 2018. Additionally, we included the 177 Lu-PSMA RLT cycles from two participating institutions from 2016 to 2020 for further validation. Results: We identified 12553 cases which were treated with 177 Lu-PSMA RLT. The number of 177 Lu-PSMA RLTs steadily increased from 1077 to 3640 therapies during the study period (+641 RLT/year; p&lt;0.005). In 2016, 25 departments of nuclear medicine offered this treatment, which increased to 44 nuclear medicine departments in 2020. In 2016, 16% of nuclear medicine departments (4/25) performed more than 100 177 Lu-PSMA RLTs, which increased to 36% (16/44) in 2020 (p&lt;0.005). In 2016, 88% (22/25) of 177 Lu-PSMA RLTs were performed at a university hospital, which decreased to 70% (31/44) in 2020. The proportion of patients older than 65 years receiving 177 Lu-PSMA RLT increased from 78% in 2016 to 81% in 2020. Conclusions: Treatment of mCRPC with 177 Lu-PSMA RLT has been rapidly increasing in Germany in the recent years providing an additional therapy option. Most of the therapies are performed at academic hospitals.
Comprehensive gene sequencing to identify progression predictors to muscle-invasive bladder cancer.
Authors: Jocelyne Brianna Cyrenne, Sindu Mary Kanjeekal, Lisa Porter, Dora Cavallo-Medved, Bre-Anne Fifield, Luis Rueda, Govindaraja Atikukke, Abedalrhman Alkhateeb, Yasser El-Gohary
Journal: Journal of Clinical Oncology (2023)

570 Background: Over 8900 Canadians are diagnosed with bladder cancer every year, ranking it the fifth most frequent cancer. It can manifest as either non-muscle invasive bladder cancer (NMIBC) or muscle invasive bladder cancer (MIBC). The majority of patients initially receive a diagnosis of NMIBC, although high-grade NMIBC has a 50–70% recurrence rate and 10–30% chance at progressing to MIBC. The transition from high-grade NMIBC to MIBC is poorly understood, and there are currently no accurate biomarkers that predict disease progression. We propose a comprehensive molecular characterization to pinpoint specific copy number alterations (CNAs) related to either MIBC or NMIBC, and hence define the molecular development. Methods: This study analyzed a public dataset from MSKCC and 30 bladder cancer patient samples from Windsor Regional Hospital, both containing NMIBC and MIBC samples. Comprehensive gene sequencing was performed, and CNAs were obtained in over 500 common tumour gene panels. Results: Preliminary data from this study found MIBC may be predicted with 91% accuracy and 95% precision using CNA values of TP53, DDR2 and MLL2. In particular, MIBC correlates with gain of DDR2 or MLL2. Importantly, it has been demonstrated that high expression of DDR2 is associated with a worse prognosis. A panel of bladder carcinoma cell lines were used to validate the DDR2 findings. DDR2 values were quantified across the panels and corresponded with proliferation and invasiveness of cell lines. DDR2 was examined as a possible therapeutic target. Conclusions: Taken together, these findings provide insight to the pathogenesis of muscle invasion in bladder cancer. The potential to identify "genomic triggers" for the transition was facilitated by creating a genetic profile at these two stages.
Association of exposure of Camp Lejeune contaminated water and prostate cancer outcomes.
Authors: Leah N. Deshler, Kylie M. Morgan, Elizabeth A. Duran, Tyler J. Nelson, Kripa Guram, Brent S Rose
Journal: Journal of Clinical Oncology (2023)

265 Background: There is evidence that exposure to contaminated water while serving at Camp Lejeune is associated with the development of genitourinary cancers including kidney and bladder; however, there is a lack of literature regarding prostate cancer (PC). We investigated disease severity at diagnosis, overall survival, and cumulative incidence of metastases for PC patients within the Veterans Health Administration (VHA) who served at Camp Lejeune. Methods: The cohort included men diagnosed with PC between 1999 and 2022 within the VHA Database. Patients who were housed at or had one or more Military Service Episodes between August 1, 1953 and December 31, 1987 at Camp Lejeune were considered to have exposure. Camp Lejeune exposure status and baseline characteristics were ascertained through the VHA electronic health records. Logistic regressions were used to analyze associations between Camp Lejeune exposure and adverse diagnostic characteristics, adjusted for demographic covariates. The outcome of metastases was identified through natural language processing from cancer or radiology documents. Time to metastases was defined as the time from PC diagnosis to metastases, with other causes of death considered as competing risks. The hazard ratio for the association between Camp Lejeune exposure and metastatic disease was calculated with a Cox regression model, controlling for covariates. The difference in overall survival was assessed with the Kaplan-Meier method and log-rank test. Results: The cohort included 6,918 men with PC, 1,635 (23.6%) of which had Camp Lejeune exposure and 5,283 (76.4%) without. Median age at diagnosis was 65 years. Logistic regression models indicated patients with Camp Lejeune exposure have similar odds of having Gleason Score ≥8 at diagnosis (odds ratio (OR) 0.97, p=0.62) and metastasis at diagnosis (OR 1.00, p=0.997), and slightly lower odds of PSA &gt;20 ng/mL at diagnosis (OR 0.78, p=0.02).There were 803 patients with metastatic disease, 159 of which had Camp Lejeune exposure in comparison to the 644 that did not. The 10-year cumulative incidence of metastases for those with Camp Lejeune exposure was 11.9% (CI: 9.9-13.9%), while for those without exposure it was 14.0% (CI: 12.8-15.1%). The Cox proportional hazards model indicated that those with Camp Lejeune exposure had a similar risk of developing metastases (hazard tatio (HR) 0.93, p=0.43) compared to those without exposure. The 10-year overall survival was similar for those with Camp Lejeune exposure (83.3% [CI: 80.7-85.9%]) compared to those without exposure (82.5% [CI: 81.1-83.9%]) (p=0.2). Conclusions: In contrast to kidney and bladder cancers, Camp Lejeune exposure is not associated with worse outcomes for PC. Further research should be conducted to test whether Camp Lejeune exposure affects the risk of developing PC. However, these data do not support Camp Lejeune exposure playing a large role in PC outcomes.
EDEN (Etude Désescalade sEmiNome): Prospective therapeutic de-escalation and miRNA-M371 biomarker evaluation phase II study for stage IIa/IIb &lt; 3 cm seminomas.
Authors: Armelle Vinceneux, David Pasquier, Ellen Blanc, Valéry Attignon, Pierre Blanchard, Aude Flechon
Journal: Journal of Clinical Oncology (2023)

TPS434 Background: At diagnosis, 10 to 15% of testicular pure seminomas have a stage II defined by the presence of retroperitoneal lymph node metastases. The optimal choice of treatment modalities are associated with excellent efficacy but also acute and late toxicities. De-escalating treatment for seminoma patients with stage IIb, IIc and III and good prognosis according to IGCCCG (International Germ Cell Cancer Collaborative Group) based on negative FDG-PET (Fluorodeoxyglucose Positron Emission Tomography) after 2 cycles of EP (etoposide, cisplatine) chemotherapy seems feasible and safe according to SEMITEP cohort 2 results (Loriot Y, and al GETUG SEMITEP Trial: Eur Urol. 2022 Aug;82(2):172-179). Serum levels of microRNA (miR)-371a-3p (miRNA-M371) have been significantly associated with clinical stage and response to treatment in testicular germ cell tumors, with sensitivity and specificity higher than those of classic markers. The aim of the study NCT05529251 is to propose a new therapeutic approach for the stages IIa/IIb. Methods: This phase II, multicenter, prospective, randomized, non-comparative, de-escalation study will include patient with primary testicular seminomatous germ cell tumor with stage IIa/IIb &lt; 3 cm in largest diameter seminoma, histologically proved after orchiectomy and good prognosis according to IGCCCG and LDH (Lactate DesHydogenase) &lt; 2.5 x Upper Limit of Normal (ULN). They must have progressive disease and no prior treatment with radiotherapy or chemotherapy. In case of negative week-3 (after 1 EP cycle) PET-scan, patients will be randomized according to 2 arms ARM A: Boost of radiotherapy 20 to 30 Gray (Gy); ARM B Carboplatin AUC7 chemotherapy. In case of positive week-3 PET-scan: 3 courses of EP chemotherapy (ARM C). Primary outcome will include progression-free rate at 36 months. Secondary Outcome Measures will be serum level of miRNA M371, correlation with response to treatments and PET scan results, overall survival (OS), quality of life and tolerance to treatment. Blood samples (miRNA-M371) will be collected at screening, at the time of randomization before second cycle of chemotherapy or radiotherapy, at the end of treatment and at relapse. Enrollment has started in October 2022. A total of 90 patients will be included in the interventional study, leading to approximately 60 patients with negative FDG-PET randomized. Clinical trial information: NCT05529251 .
Clinical outcomes of abiraterone acetate (AA) or enzalutamide (E) as first-line therapy (Rx) for men aged ≥75 with metastatic castration-resistant prostate cancer (mCRPC) according to previous use of docetaxel (D) for metastatic castration-sensitive prostate cancer (mCSPC) in a multicenter international registry: A SPARTACUSS – Meet-URO 26 study.
Authors: Richard M. Lee-Ying, Calogero Saieva, Pier Vitale Nuzzo, Andrea Malgeri, Giuseppe Fotia, Elisa Zanardi, Sabrina Rossetti, Loana Bueno Valenca, Anna Patrikidou, Mikol Modesti, Thiago Martins Oliveira, Sandro Pignata, Giuseppe Fornarini, Giuseppe Procopio, Daniele Santini, Christopher Sweeney, Daniel Yick Chin Heng, Ugo De Giorgi, Antonio Russo, Edoardo Francini
Journal: Journal of Clinical Oncology (2023)

107 Background: The optimal management of mCRPC in men aged ≥75 is challenging, and there is a paucity of clinical data in the literature. Although AA and E are commonly used as 1 st line Rx for mCRPC, it is unclear whether use of upfront D for mCSPC may impact their clinical efficacy or safety in this elderly population. Methods: Patients aged ≥75 who started AA or E as 1 st line Rx for mCRPC within January 2015 - April 2019 were identified from the IRB approved databases of 10 institutions in Europe, South and North America. Demographic and clinicopathological data were collected from available medical records, including Gleason, prior local therapy, newly diagnosed metastatic disease, disease volume, ECOG, PSA and sites of metastases. Patients were classified by use of upfront D for mCSPC. The primary endpoints were overall survival (OS) from AA/E onset and OS from ADT start and safety of AA/E. The endpoints distributions including median (95% CI) were estimated by Kaplan-Meier method. Results: Of the 337 patients selected, 24 (7.1%) received ADT+D and 313 (92.9%) ADT alone for mCSPC. Patients with ADT+D tended to be younger (78 vs 81, p=0.022) and, albeit not statistically significant, had higher rates of Gleason score &gt;8 (81.0% vs 62.6%, p=0.10), newly diagnosed (83.3% vs 65.6%, p=0.08) and high volume disease (45.8% vs 34.6%, p=0.28), compared to those with ADT alone. Median follow-up was 18.8 months. No significant difference of OS from ADT start or from AA/E onset was observed between the 2 cohorts (see table). Despite OS from ADT start being longer in those having ADT+D, OS from AA/E start was approximately 2 years in both cohorts. Rates of adverse events (AEs) of any grade (58.3% vs 52.1%, p=0.67) and grade ≥3 (12.5% vs 15.7%, p=1.0) did not significantly differ between the 2 cohorts. Conclusions: While limited by small sample size for ADT+D and retrospective study design, patients aged ≥75 having AA/E as 1 st line mCRPC Rx showed similar survival outcomes and tolerability regardless of previous use of D for mCSPC. [Table: see text]